chr1-6218354-A-G

Variant names:

• chr1-6218354-A-G
• rs709209
• NM_207396.3:c.1718A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_207396.3(RNF207):​c.1718A>G​(p.Asn573Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 1,611,076 control chromosomes in the GnomAD database, including 109,978 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (16854 hom., cov: 33)
  • Exomes 𝑓: 0.35 (93124 hom.)
• Consequence: RNF207 NM_207396.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.309
• Publications: 44 publications found

Genes affected

RNF207 (HGNC:32947): (ring finger protein 207) Enables Hsp70 protein binding activity; chaperone binding activity; and transmembrane transporter binding activity. Involved in positive regulation of delayed rectifier potassium channel activity; positive regulation of gene expression; and positive regulation of voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization. Located in perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

RNF207 Gene-Disease associations (from GenCC):

• long QT syndrome

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.5483464E-6).
• BP6: Variant 1-6218354-A-G is Benign according to our data. Variant chr1-6218354-A-G is described in ClinVar as Benign. ClinVar VariationId is 1274153.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF207	NM_207396.3	c.1718A>G	p.Asn573Ser	missense_variant	Exon 17 of 18	ENST00000377939.5	NP_997279.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF207	ENST00000377939.5	c.1718A>G	p.Asn573Ser	missense_variant	Exon 17 of 18	5	NM_207396.3	ENSP00000367173.4
RNF207	ENST00000483336.1	n.350A>G		non_coding_transcript_exon_variant	Exon 3 of 4	3
RNF207	ENST00000496676.5	n.1435A>G		non_coding_transcript_exon_variant	Exon 9 of 10	2

Frequencies

GnomAD3 genomes AF: 0.437 AC: 66381 AN: 152000 Hom.: 16810 Cov.: 33

Gnomad AFR AF: 0.710

Gnomad AMI AF: 0.403

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.265

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.421

GnomAD2 exomes AF: 0.349 AC: 86771 AN: 248648 AF XY: 0.352

Gnomad AFR exome AF: 0.716

Gnomad AMR exome AF: 0.229

Gnomad ASJ exome AF: 0.330

Gnomad EAS exome AF: 0.253

Gnomad FIN exome AF: 0.295

Gnomad NFE exome AF: 0.343

Gnomad OTH exome AF: 0.354

GnomAD4 exome AF: 0.349 AC: 509530 AN: 1458958 Hom.: 93124 Cov.: 31 AF XY: 0.351 AC XY: 254635 AN XY: 725910

African (AFR) AF: 0.725 AC: 24211 AN: 33398

American (AMR) AF: 0.242 AC: 10796 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 8558 AN: 26110

East Asian (EAS) AF: 0.292 AC: 11577 AN: 39670

South Asian (SAS) AF: 0.415 AC: 35782 AN: 86168

European-Finnish (FIN) AF: 0.294 AC: 15683 AN: 53358

Middle Eastern (MID) AF: 0.417 AC: 2402 AN: 5754

European-Non Finnish (NFE) AF: 0.342 AC: 378925 AN: 1109568

Other (OTH) AF: 0.358 AC: 21596 AN: 60256

GnomAD4 genome AF: 0.437 AC: 66474 AN: 152118 Hom.: 16854 Cov.: 33 AF XY: 0.434 AC XY: 32298 AN XY: 74346

African (AFR) AF: 0.710 AC: 29455 AN: 41482

American (AMR) AF: 0.329 AC: 5032 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 1114 AN: 3470

East Asian (EAS) AF: 0.264 AC: 1366 AN: 5166

South Asian (SAS) AF: 0.404 AC: 1949 AN: 4826

European-Finnish (FIN) AF: 0.298 AC: 3157 AN: 10580

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.339 AC: 23030 AN: 67988

Other (OTH) AF: 0.422 AC: 893 AN: 2114

Alfa AF: 0.376 Hom.: 37197

Bravo AF: 0.448

TwinsUK AF: 0.347 AC: 1288

ALSPAC AF: 0.346 AC: 1333

ESP6500AA AF: 0.680 AC: 2908

ESP6500EA AF: 0.336 AC: 2857

ExAC AF: 0.361 AC: 43664

Asia WGS AF: 0.404 AC: 1408 AN: 3478

EpiCase AF: 0.354

EpiControl AF: 0.349

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 13, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 28379579, 29874175) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.052
BayesDel_addAF	Benign	-0.86	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.31
DANN	Benign	0.26
DEOGEN2	Benign	0.00063	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0064	N
LIST_S2	Benign	0.19	T
MetaRNN	Benign	0.0000025	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-1.2	N
PhyloP100		-0.31
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.58	N
REVEL	Benign	0.023
Sift	Benign	1.0	T
Sift4G	Benign	0.72	T
Polyphen		0.0	B
Vest4		0.026
MPC		0.13
ClinPred		0.0011	T
GERP RS		-1.3
Varity_R		0.018
gMVP		0.053
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs709209; hg19: chr1-6278414; COSMIC: COSV59473074; COSMIC: COSV59473074;